Brown has almost 600 faculty/researchers in the Division of Biology and Medicine;it received $112,884,965 in NIH support in 2008, it has a strong translational and clinical research group, and a basic research emphasis on genomic applications. Yet this institution has limited DNA sequencing capabilities i.e. a single Applied Biosystems 3130xl Genetic Analyzer capillary sequencer. The research frontier has changed tremendously so that now DNA sequencing is used for exploration, for detailed analysis, and for quantitation. It is even cost effective now compared to many microarray approaches for analysis of e.g. whole genome transcriptome arrays. Investigators at Brown University are experiencing a burgeoning need for rapid, deep, and cost-effective DNA sequencing. An assessment of needs has coalesced to the High Throughput DNA Sequencing instruments;such an instrument would meet the vast majority of research needs. Unfortunately, the queues for off-site facilities ranged from 4 weeks (providing the investigator made all their own libraries), to over 2 months for full-service facilities. An off-campus sample was also subject to consistently getting delayed by new on-campus projects. We therefore request support to acquire a high-throughput DNA sequencer to handle the burgeoning needs for DNA sequencing in the Division of Biology and Medicine at Brown University. Historically, the short read sequencers (Solexa, SOLID) have been attractive for the high throughput and relatively low cost of sequence. However, they have lagged behind in their potential because of the difficulties in interpreting and aligning short sequencing reads, 25-35 bases in length, of metazoan genomes with large sequence complexity. This detraction is minimized now with the Illumina GAII platform, achieving read lengths of over 100 bases on average, and with paired end read capabilities included in this next generation unit, the read lengths now approach the lengths of alternative sequencing formats, e.g. 454 lengths, but with much higher throughput and significantly lower cost. Indeed, with new sequencing chemistries, and advances in software capabilities, de novo sequencing is added to its list of capabilities, making this type of instrument meet the investigator need at Brown University. This application represents the collective DNA sequencing needs of 32 major users and 9 minor users, representing 14 different research departments, and over 70 NIH grants. It contains a mix of basic and clinical researchers, M.D.s and Ph.D.s. Importantly, it contains a strong contingent of computational molecular biologists interested in better, and more easily making use of the large data sets resulting from such an instrument. The University is committed to supporting this instrument through personnel, laboratory space, computer data storage capabilities, and extended service contracts to maximize the investment of the instrument and to facilitate the output of each investigator.